The drug pentoxifylline is indicated for improving the flow properties of blood by decreasing its viscosity. For patients with chronic peripheral arterial disease, the administration of pentoxifylline increases the blood flow to the affected microcirculation and enhances tissue oxygenation. In therapy, tissue oxygen levels are increased by administering therapeutic doses of pentoxifylline to patients with peripheral arterial disease. The drug pentoxifylline is used for the treatment of claudication as accompanied by chronic occlusive arterial disease.
A critical need exists for a dosage form for the controlled-rate administration of pentoxifylline, which drug is administered presently in conventional pharmaceutical forms, such as tablets and capsules. The conventional forms deliver their drug by dumping and this leads to uneven dosing of drug, to uneven blood levels of the drug characterized by peaks and valleys, and accordingly this does not provide controlled-rate therapy over an extended period of time. Presently, pentoxifylline is administered two or three times a day because pentoxifylline and pentoxifylline metabolites have short half-lives of 0.4 to 0.8 hours and 1.0 to 1.6 hours respectively. The prior art dosing patterns and the half-life characteristics of pentoxifylline dictate of the need for a dosage form that can administer pentoxifylline at a controlled rate over an extended time to provide continuous therapy and enhanced patient therapy. The drug pentoxifylline is known in Physician's Desk Reference, 47 Edition, 1993, pages 1125 to 1126, published by Medical Economics Data, Montvale, N.J.
The prior art provided a dosage form that can administer a drug for continuous therapy. For example, in U.S. Pat. No. 4,327,725 issued to Cortese and Theeuwes, and in U.S. Pat. Nos. 4,612,008; 4,765,989; and 4,783,337 issued to Wong, Barclay, Deters and Theeuwes a dosage form is disclosed that provides therapy affected by a high osmotic pressure generated inside the dosage form. The dosage form of these patients operate successfully for delivering a drug that develops a high osmotic pressure gradient across a semipermeable membrane. The drug pentoxifylline however, possesses a low osmotic pressure of about 6 to 6.5 atmospheres, which dictates against providing an osmotic dosage form for use in the gastrointestinal tract. The gastrointestinal tract has a higher osmotic pressure environment, and this adversely affects the delivery of pentoxifylline from a dosage form in this environment.
It is immediately apparent in the light of the above presentation, that an urgent need exists for a dosage form endowed with physical-chemical properties for delivering pentoxifylline. The need exists for a dosage form for delivering pentoxifylline at a controlled-rate in a continuous dose in a therapeutic range while simultaneously providing the beneficial therapy. It will be appreciated by those versed in the drug dispensing art, that if such a dosage form is provided that can administer pentoxifylline in the desired delivery program, the dosage form would represent an advancement and a valuable contribution in the dispensing art.